How Enzymatic Platforms May Change the Therapeutic RNA Supply Chain

Codexis, a provider of enzymatic solutions, and Nitto Denko Avecia, a contract development and manufacturing organization (CDMO), will explore the potential role of Codexis’s ECO Synthesis manufacturing platform in producing therapeutic small interfering RNA (siRNA) in a newly signed evaluation agreement (1). The collaboration underscores a growing interest in alternative manufacturing pathways as the demand for oligonucleotide therapeutics continues to increase (2).

Under the agreement, Nitto Denko Avecia will assess the applicability of the ECO Synthesis platform within its established development and production operations. Oligonucleotide therapeutics, including siRNA, remain constrained by the scalability limits of traditional solid-phase synthesis. Enzymatic synthesis methods such as ECO Synthesis are being considered across the sector as companies look for ways to improve sustainability, efficiency, and cost structures in clinical and commercial supply chains, according to an Oct. 29, 2025 company press release.

“We are excited to partner with Nitto Denko Avecia, a recognized leader in therapeutic oligonucleotide manufacturing,” said Stephen Dilly, MBBS, PhD, chairman and chief executive officer, Codexis, in the release (1). “This collaboration represents a significant milestone toward expanding the reach of our ECO Synthesis [m]anufacturing [p]latform, through best-in-class CDMO collaborations.”

How could enzymatic manufacturing improve oligonucleotide scale-up?

Codexis’s manufacturing platform offers an alternative to established solid-phase chemical methods that have long been the backbone of oligonucleotide production. Solid-phase synthesis has supported the approval and commercialization of multiple RNA-targeted medicines, but the approach can face challenges as volumes increase, particularly in cost, reagent use, and waste generation (3).

The company has developed enzymatic technologies used in multiple therapeutic manufacturing settings. The evaluation agreement enables Nitto Denko Avecia to determine whether the ECO Synthesis platform could provide operational or technical advantages as the complexity and quantity of siRNA candidates continue to grow.

“At Nitto Denko Avecia, we are constantly looking to the future of oligonucleotide manufacturing,” said Tammy Cooper, president, Nitto Denko Avecia, in the release. “Exploring Codexis’ [manufacturing platform] reflects our commitment to pioneering next-generation technologies that can redefine scalability, sustainability, and innovation in therapeutic development.”

Why does this collaboration matter for future therapeutic RNA production?

Enzymatic synthesis has gained increased attention in recent years because of its potential to support large-scale production while reducing the environmental impact associated with current methods. Any progress toward more flexible and resource-efficient manufacturing could influence how the industry approaches the expansion of siRNA pipelines, particularly as more programs reach later development stages (4,5).

For Nitto Denko Avecia and others in the CDMO space, evaluating technologies like ECO Synthesis provides insight into future facility and process needs. For therapeutic developers, a broader set of manufacturing options may help reduce risk in commercial planning.

By combining Codexis’s enzymatic manufacturing technology with Nitto Denko Avecia’s experience producing more than 1500 oligonucleotide sequences across its US facilities, this collaboration contributes to the movement toward advanced and potentially more scalable siRNA supply strategies (1). As oligonucleotide therapeutics become increasingly integral in the treatment of genetic and rare diseases, manufacturing innovations will remain central to ensuring reliable access and global availability (6).

References

1. Codexis. Codexis and Nitto Denko Avecia Enter Evaluation Agreement to Explore Codexis’s ECO Synthesis Manufacturing Platform for Therapeutic siRNA Manufacturing. Press Release. Oct. 29, 2025.
2. Obexer, R.; Nassir, M.; Moody, E. R.; Baran, P. S.; Lovelock, S. L. Modern Approaches to Therapeutic Oligonucleotide Manufacturing. Science 2024, 384, eadl4015. DOI: 10.1126/science.adl4015
3. Andrews, B. I.; Antia, F. D.; Brueggemeier, S. B.; et al. Sustainability Challenges and Opportunities in Oligonucleotide Manufacturing. J. Org. Chem. 2021, 86 (1), 49–61. DOI: 10.1021/acs.joc.0c02291
4. Pichon, M.; Hollenstein, M. Controlled Enzymatic Synthesis of Oligonucleotides. Commun. Chem. 2024, 7, 138. DOI: 10.1038/s42004-024-01216-0
5. Zhang, B.; Du, Y.; Zhang, J. A Solid-Phase Enzymatic Synthesis Platform for the Facile Production of 2′-Fluoroarabinonucleic Acid (FANA) and Chimeric XNA Oligonucleotides Using an Evolved XNA Polymerase. Nucleic Acids Res. 2025, 53 (12), gkaf567. DOI: 10.1093/nar/gkaf567
6. Cassey, B. Oligonucleotide Manufacturing Innovation: Challenges, Risks, and Opportunities. Nucleic Acid Insights 2025, 2 (5), 109–115. DOI: 10.18609/nuc.2025.018